Patient Information Leaflet

Tresiba 100 units/mL FlexTouch pre-filled injectable pen

insulina degludec

Read this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, talk to your doctor, pharmacist or nurse, even if they are not listed in this leaflet. See section 4.

6. Contents of the pack and additional information

Tresiba is a long-acting basal insulin called insulin degludec. It is used in adults, adolescents, and children one year of age and older to treat diabetes mellitus. Tresiba helps the body to lower blood sugar levels. It is used once a day. When the usual administration time cannot be followed, the administration time can be varied because Tresiba has a prolonged hypoglycemic effect (see section 3, “Flexibility in administration schedule”). Tresiba can be used with rapid-acting insulins administered in relation to meals. In patients with type 2 diabetes mellitus, Tresiba may be used in combination with oral diabetes medications or with non-insulin injectable antidiabetic drugs.

In patients with type 1 diabetes mellitus, Tresiba must be used always in combination with rapid-acting insulins administered in relation to meals.

Do not use Tresiba

• if you are allergic to insulin degludec or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Consult your doctor, pharmacist or nurse before starting to use Tresiba. It is important that you know the following information:

• Low blood sugar (hypoglycaemia) – If your blood sugar level is too low, follow the instructions in section 4.
• High blood sugar (hyperglycaemia) – If your blood sugar level is too high, follow the instructions in section 4.
• Switching from other insulins – You may need to adjust your insulin dose if you switch from another type, brand or manufacturer of insulin. Talk to your doctor.
• Use of Pioglitazona with insulin – See the section “Pioglitazona” below.
• Visual disturbances – A sudden improvement in blood sugar control may cause a temporary worsening of visual disturbances due to diabetes. If you experience any problems with your vision, talk to your doctor.
• Use of the correct insulin – Always check the label of your insulin before each injection to avoid confusion between the different concentrations of Tresiba and other insulins.

See section 3 if you have reduced vision.

Changes in the skin at the injection site

The injection site should be rotated to help avoid changes in the fatty tissue such as thickening of the skin, shrinkage of the skin or lumps under the skin. Insulin may not work well if injected into a thickened, shrunk or lumpy area (see section 3 “How to use Tresiba”). Inform your doctor if you detect any changes in the injection site. Inform your doctor if you are currently injecting into these affected areas, before starting to inject into a different area. Your doctor may advise you to check your blood sugar levels more closely, and adjust your insulin or the dose of your other diabetes medicines.

Children and adolescents

Tresiba can be used in adolescents and children from 1 year of age. There is no experience with the use of Tresiba in children under 1 year of age.

Other medicines and Tresiba

Inform your doctor, pharmacist or nurse if you are using, have used recently or may need to use any other medicine. Some medicines affect blood sugar levels, requiring a change in your insulin dose.

The following are the main medicines that can affect your treatment with insulin:

Your blood sugar level may decrease (hypoglycaemia) if you take:

• other diabetes medicines (oral and injectable)
• sulfonamides, to treat infections
• anabolic steroids, such as testosterone
• beta-blockers, to treat high blood pressure. These may make it harder to recognise the warning signs of low blood sugar (see section 4 “Warning signs of low blood sugar”)
• aspirin (and other salicylates), for pain and mild fever
• monoamine oxidase inhibitors (MAOIs), to treat depression
• angiotensin-converting enzyme (ACE) inhibitors, to treat certain heart problems or high blood pressure.

Your blood sugar level may increase (hyperglycaemia) if you take:

• danazol, to treat endometriosis
• oral contraceptives (birth control pill)
• thyroid hormones, to treat thyroid problems
• growth hormone, to treat a deficiency of this hormone
• glucocorticoids, such as cortisone, to treat inflammation
• sympathomimetics, such as adrenaline (epinephrine), salbutamol or terbutaline, to treat asthma
• thiazides, to treat high blood pressure or if your body retains too much fluid.

Octreotide and lanreotide: used to treat acromegaly, a rare disorder characterised by excessive production of growth hormone. These medicines may increase or decrease your blood sugar levels.

Pioglitazona: oral antidiabetic medicine used to treat type 2 diabetes. Some patients with long-standing type 2 diabetes and pre-existing heart disease or stroke who were treated with pioglitazona and insulin developed heart failure. Inform your doctor immediately if you experience signs of heart failure such as unusual shortness of breath, rapid weight gain or localised inflammation (oedema).

If you are in any of the above situations (or are unsure), consult your doctor, pharmacist or nurse.

Use of Tresiba with alcohol

If you drink alcohol, it may change your need for insulin as your blood sugar level may be increased or decreased. Therefore, you should monitor your blood sugar level more frequently than usual.

Pregnancy and lactation

If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor or pharmacist before using this medicine. You may need to adjust your insulin dose while pregnant and after delivery. During pregnancy, careful control of your diabetes is necessary. Avoiding low blood sugar (hypoglycaemia) is especially important for the health of your baby.

Driving and using machines

Low or high blood sugar may affect your ability to drive or use tools or machines. If your blood sugar level is too low or too high, your concentration and reaction time may be affected. This could put your life or the lives of others at risk. Ask your doctor if you can drive if:

• you experience frequent episodes of hypoglycaemia;
• you find it difficult to recognise the warning signs of hypoglycaemia.

Important information about some of the components of Tresiba

This medicine contains less than 1 mmol of sodium (23 mg) per dose, which is essentially “sodium-free”.

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, consult your doctor, pharmacist, or nurse again.

If you are blind or have reduced vision and cannot read the dose counter on the pen, do not use this pen without help. Ask for help from a person without vision problems and trained in the use of the FlexTouch pre-filled pen.

Tresiba in pre-filled pen is available in two doses. “Tresiba 100 units/ml” or “Tresiba 200 units/ml” is clearly indicated on the pen label and carton. Additionally, the carton and label of Tresiba 100 units/ml are light green and the carton and label of Tresiba 200 units/ml are dark green with stripes and a red box highlighting the dose.

For both doses, the necessary dose is selected in units. However, the dose units vary between the two doses of Tresiba.

The pre-filled pen of 100 units/ml can provide a dose of 1–80 units in an injection, in increments of 1 unit. The dose counter on the pre-filled pen shows the number of units of insulin to be injected. Do not make any dose calculations.

Your doctor will decide with you:

• what amount of Tresiba you will need each day
• when to check your blood sugar level and if you need a higher or lower dose.

Flexibility in administration schedule

• Always follow the usage recommendations of your doctor.
• Use Tresiba once a day, preferably at the same time every day.
• In some cases, when it is not possible to use Tresiba at the same time of day, you can use it at a different time of day. Make sure that there is a minimum of 8 hours between doses. There is no experience with flexibility in administration schedule of Tresiba in children and adolescents.
• If you want to modify your usual diet, consult your doctor, pharmacist, or nurse beforehand, as a change in diet may alter your need for insulin.

Your doctor may change your dose based on your blood sugar level.

When using other medications, ask your doctor if you need to adjust your treatment.

Use in elderly patients (≥65 years)

Tresiba can be used in elderly patients, but if you are an elderly patient, you may need to check your blood sugar level more frequently.

Use in patients with renal or hepatic problems

If you have renal or hepatic problems, you may need to monitor your blood sugar level more frequently. Talk to your doctor about possible changes in your dose.

Medication injection

Before using Tresiba for the first time, your doctor or nurse will show you how to use the pre-filled pen.

• Check the name and concentration on the pen label to ensure that it is Tresiba 100 units/ml.

Do not use Tresiba

• in insulin infusion pumps.
• if the pen has been damaged or not stored properly (see section 5).
• if the insulin does not have a transparent and colorless appearance.

How to inject

• Tresiba is injected under the skin (subcutaneous injection). Do not inject it into a vein or muscle.
• The best areas for injection are the front of the thigh, the upper arm, and the front of the abdomen (abdomen).
• Change the injection site every day to reduce the risk of developing lumps and depressions in the skin (see section 4).
• Always use a new needle for each injection. Reusing needles may increase the risk of blockage, leading to inaccurate dosing. Dispose of the needle safely after each use.
• Do not use a syringe to extract the solution from the pen to avoid dosing errors and possible overdoses.

On the other side of this leaflet, detailed usage instructions are provided.

If you use more Tresiba than you should

If you use too much insulin, your blood sugar level may drop too low (hypoglycemia), see the advice in section 4 “Blood sugar level too low”.

If you forget to use Tresiba

If you forget to administer a dose, inject the missed dose as soon as you remember, ensuring a minimum of 8 hours between doses. If you discover that you have forgotten the previous dose at the time of injecting the next dose, do not inject a double dose, inject your usual daily dose.

If you interrupt treatment with Tresiba

Do not stop treatment with your insulin without consulting your doctor. Stopping insulin administration could cause high blood sugar levels and diabetic ketoacidosis (a condition that consists of an excessive amount of acid in the blood), see the advice in section 4 “Blood sugar level too high”.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

When you are being treated with insulin, you may experience hypoglycemia (low blood sugar) very frequently (it may affect more than 1 in 10 people). It can be very serious. If your blood sugar level drops too low, you may lose consciousness. Severe hypoglycemia can cause brain damage and be potentially fatal. If you experience symptoms of low blood sugar, take measures to increase your blood sugar level immediately. See the "Low Blood Sugar" guidelines.

If you experience a severe allergic reaction (rarely) to insulin or any of the components of Tresiba, stop treatment with this medicine and consult your doctor immediately. The signs of a severe allergic reaction are:

• The local reactions spread to other parts of the body.
• You feel suddenly unwell with sweating.
• You start to feel dizzy (vomiting).
• You experience difficulty breathing.
• You have palpitations or feel dizzy.

Changes in skin at the injection site:

If you inject insulin into the same place, the fatty tissue may shrink (lipoatrophy) or become thicker (lipohypertrophy) (it may affect up to 1 in 100 people). Bumps under the skin may also occur due to the accumulation of a protein called amyloid (cutaneous amyloidosis; it is not known how often this occurs). The insulin may not work very well if injected into a thickened, shrunk, or swollen area. Change the injection site to help prevent these skin changes.

Other side effects include:

Frequent(it may affect up to 1 in 10people)

Local reactions: local reactions may occur at the injection site. Symptoms may include: pain, redness, rashes, inflammation, and itching. These reactions usually disappear after a few days. If symptoms do not disappear after a few weeks, consult your doctor. If reactions worsen, stop treatment with Tresiba and consult your doctor immediately. For more information, see "Severe Allergic Reaction" above.

Infrequent(it may affect up to 1 in 100people)

Joint inflammation: when starting to use the medicine, the body may retain more fluid than it should. This causes inflammation of the ankles and other joints. This effect usually disappears quickly.

Rare(it may affect up to 1 in 1,000people)

This medicine may cause allergic reactions such as rashes, swelling of the tongue and lips, diarrhea, nausea, fatigue, and pruritus.

General effects of diabetes treatment

• Low blood sugar (hypoglycemia)

You may experience low blood sugar levels if:

You drink alcohol, inject too much insulin, exercise more than usual, eat very little, or skip a meal.

Warning signs of low blood sugar, which may appear suddenly:

Headache, difficulty speaking, palpitations, cold sweat, pale and cold skin, dizziness, excessive hunger, tremors, nervousness or concern, fatigue, weakness, and unusual drowsiness, confusion, difficulty concentrating, and temporary changes in vision.

What to do if your blood sugar level is too low

• Take glucose tablets or a sweet product, such as candies, cookies, or fruit juice (always carry glucose tablets or sweet products with you, just in case you need them).
• Measure your blood sugar level if possible and then rest. You may need to measure your blood sugar level more than once, as with all basal insulins, recovery may be delayed.
• Wait until the hypoglycemia symptoms have disappeared or your blood sugar level has stabilized. Then continue with your insulin treatment as usual.

What others should do if you lose consciousness

Inform the people you spend time with that you have diabetes. Tell them what the consequences of low blood sugar levels may be, including the risk of losing consciousness.

Inform them that, if you become unconscious, they should:

• Turn you onto your side.
• Seek immediate medical assistance.
• Do notgive you anything to eat or drink, as you may choke.

You may recover consciousness more quickly if you receive glucagon. This should only be administered by someone who knows how to do it.

• If you are given glucagon, you should take glucose or a sweet product as soon as you regain consciousness.
• If you do not respond to glucagon treatment, you should be treated in a hospital.
• If severe hypoglycemia is not treated, it may cause brain damage over time. This may be temporary or permanent. It may even cause death.

Talk to your doctor if:

• You have experienced blood sugar levels that are too low and you have lost consciousness.
• You have needed glucagon.
• You have experienced several low blood sugar levels recently.

You may need to adjust the dose or frequency of your insulin injections, diet, or exercise.

• High blood sugar (hyperglycemia)

You may experience high blood sugar levels if:

You eat more or exercise less than usual, drink alcohol, have an infection or fever, do not inject enough insulin, repeatedly inject less insulin than you need, forget to inject insulin, or interrupt insulin treatment without talking to your doctor.

Warning signs of high blood sugar, which usually appear gradually:

Dry and red skin, drowsiness or fatigue, dry mouth, fruity-smelling breath (acetone), increased need to urinate, thirst, loss of appetite, nausea, or vomiting.

These may be symptoms of a very serious condition called ketoacidosis. This is an accumulation of acid in the blood due to the body metabolizing fat instead of sugar. If not treated, it may cause diabetic coma and death.

What to do if your blood sugar level is too high

• Check your blood sugar level.
• Check the level of ketones in your urine or blood.
• Seek immediate medical assistance.

Reporting side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this prospectus. You can also report them directlythrough thenational notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the label and on the pen after “CAD”. The expiration date is the last day of the month indicated.

Before first use

Store in refrigerator (between 2°C and 8°C). Do not freeze. Keep the pen away from the freezer. Store the pen with the cap on to protect it from light.

Once opened or if carrying as a spare

You may carry your Tresiba (FlexTouch) preloaded pen with you and store it at room temperature (not above 30°C) or in refrigerator (between 2°C and 8°C) for up to 8 weeks.

Always store the pen with the cap on when not in use to protect it from light.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medicines that you no longer need. This will help protect the environment.

Composition of Tresiba

• The active ingredient is insulin degludec. Each milliliter of solution contains 100 units of insulin degludec. Each pre-filled pen contains 300 units of insulin degludec in 3 milliliters of solution.

• The other components are glycerol, metacresol, phenol, zinc acetate, hydrochloric acid, and sodium hydroxide (for pH adjustment) and water for injection (see section 2).

Appearance of the product and contents of the pack

Tresiba is presented as a transparent and colorless injectable solution in a pre-filled pen (300 units per 3 milliliters).

Pack sizes of 1 (with or without needles), 5 (without needles) and a multiple pack of 10 (2 x 5) (without needles) pre-filled pens of 3 milliliters. Some pack sizes may only be marketed.

Marketing Authorization Holder

Novo Nordisk A/S

Novo Alle 1

DK-2880 Bagsvaerd, Denmark

Responsible for manufacturing

Novo Nordisk A/S

Novo Alle 1

DK-2880 Bagsvaerd

Denmark

Novo Nordisk Production SAS

45, Avenue d’Orléans

28000 Chartres

France

Date of the last revision of this leaflet:

The detailed information on this medicine is available on the website of the European Medicines Agency:http://www.ema.europa.eu

Instructions for use of Tresiba 100 units/ml FlexTouch injectable solution in a pre-filled pen

Read these instructions carefully before using your FlexTouch pen.If you do not follow the instructions carefully, you may administer too little or too much insulin, which could produce a level of blood sugar that is too high or too low.

Do not use the pen without having received proper training from your doctor or nurse.

Start by checking the pen to ensure that it contains Tresiba 100 units/ml and then observe the illustrations to familiarize yourself with the different parts of the pen and the needle.

If you are blind or have impaired vision and cannot read the dose counter on the pen, do not use this pen without assistance.Seek the help of a person who can see well and is trained in the use of the FlexTouch pen.

Your pen is an insulin dosing pen that contains 300 units of insulin. You can select a maximum of 80 units per administration, in increments of 1 unit.

The pen is designed to be used with single-use NovoTwist or NovoFine needles up to 8 mm in length.

Important information

Pay special attention to these notes because they are important for the correct use of the pen.

1 Preparing the pen

• Check the name and concentration on the label of your pen to ensure that it contains Tresiba 100 units/ml.This is especially important if you use more than one type of insulin. If you use the wrong type of insulin, your blood sugar level may become too high or too low.

• Remove the pen cap.

• Check that the insulin in the pen has a transparent and colorless appearance.

Look through the insulin window. If the insulin has a cloudy appearance, do not use the pen.

• Take a new needle and remove the paper tab.

• Insert the needle straight into the pen. Screw it on until it is tight.

• Remove the outer needle cap and set it aside. You will need it later.It is necessary to remove the needle from the pen correctly.

• Remove the inner needle cap and discard it. If you try to put it back on, you may accidentally prick yourself with the needle.

You may see a drop of insulin at the tip of the needle. This is normal, but you must still check the insulin flow.

Always use a new needle for each injection.

This reduces the risk of contamination, infection, insulin loss, needle blockage, and inaccurate dosing.

Never use bent or damaged needles.

2 Checking the insulin flow

• Always check the insulin flow before starting.

This will help ensure that you receive the full dose of insulin.

• Turn the dose selector until you select 2 units. Make sure a 2 appears on the dose counter.

• Hold the pen with the needle pointing upwards.

Gently tap the top of the pen a few times to allow any air bubbles to rise.

• Press and hold the dose button until the dose counter returns to 0.

The 0 should be aligned with the dose marker.

You should see a drop of insulin at the tip of the needle.

You may see a small air bubble at the tip of the needle, but it will not be injected.

If no drop appears,repeat steps 2A to 2C up to 6 times. If no drop still appears, change the needle and repeat steps 2A to 2C once more.

If, despite this, no drop of insulin appears,discard the pen and use a new one.

• Always make sure a drop appears at the tip of the needle before injecting.

This ensures that the insulin is flowing.

If no drop appears,noinsulin will be injected, although the dose counter may move. This may indicate that the needle is blocked or damaged.

• Always check the flow before injecting.

If you do not check the flow, you may receive an insufficient or non-existent dose of insulin.

This may produce a level of blood sugar that is too high.

3 Selecting the dose

• Make sure the dose counter shows 0 before starting.

The 0 should be aligned with the dose marker.

• Turn the dose selector to select the dose you need, following the instructions of your doctor or nurse.

If you have selected the wrong dose, you can turn the dose selector forward or backward until you select the correct dose.

The pen can select up to a maximum of 80 units.

The dose selector changes the number of units. Only the dose counter and the dose marker show how many units you have selected for each administration.

You can select 80 units per administration as a maximum. When the pen contains less than 80 doses, the dose counter stops when it reaches the number of units remaining.

The dose selector makes a different click when turned forward, backward, or when passing the remaining number of units. Do not count the clicks of the pen.

Before injecting the insulin, always use the dose counter and the dose marker to see how many units you have selected.

Do not count the clicks of the pen. If you select the wrong dose and inject it, your blood sugar level may become too high or too low.

Do not use the insulin scale, as it only shows the approximate amount of insulin remaining in the pen.

4 Injecting the dose

• Insert the needle under the skinas your doctor or nurse has taught you.

• Make sure you can see the dose counter.

Do not touch the dose counter with your fingers. This may interrupt the injection.

• Press and hold the dose button until the dose counter returns to 0.

The 0 should be aligned with the dose marker.

You may hear or feel a click at this point.

• Keep the needle under the skin for at least 6 secondsto ensure that the full dose is administered.

• Keeping the needle and pen straight, remove them from the skin.
  If blood appears at the injection site, press gently with an absorbent pad. Do not rub the area.

You may see a drop of insulin at the tip of the needle after the injection. This is normal and does not affect the dose.

Always observe the dose counter to see how many units you inject.

The dose counter shows the exact number of units. Do not count the clicks of the pen. Press and hold the dose button until the dose counter returns to 0 after the injection. If the dose counter stops before reaching 0, the full dose has not been administered, which may result in a level of blood sugar that is too high.

5 After the injection

• Insert the tip of the needle into the outer needle cap,placed on a flat surface, withouttouching the needle or the outer needle cap.

• When the needle is covered,press the outer needle cap firmly and carefully.

• Unscrew the needleand discard it carefully.

• Put the capon the pen after each use to protect the insulin from light.

Always discard the needle after each injectionin an appropriate sharps container.This reduces the risk of contamination, infection, insulin loss, needle blockage, and inaccurate dosing. If the needle is blocked,noinsulin will be injected.

When the pen is empty, discard itwithoutthe needle attached, following the instructions of your doctor, nurse, pharmacist, or local authorities. Do not throw the used needle in the household waste.

Never try to put the inner needle cap back on.You may prick yourself withit.

Always remove the needle after each injectionand store your pen without the needle attached.

This reduces the risk of contamination, infection, insulin loss, needle blockage, and inaccurate dosing.

6 How much insulin is left?

• Theinsulin scaleshows the approximate amountof insulinremaining in the pen.

• To know exactly how much insulin is left,use the dose counter:

Turn the dose selector until thedose counterstops.

If it shows 80, it means there areat least 80units remaining in the pen.

If it showsless than 80,the number indicates the amount of units remaining in the pen.

• Turn the dose selector backward until the dose counter shows 0.

• If you need more insulin than the units remaining in the pen, you can divide the dose between two pens.

Be very careful to make the calculation correctly if you divide your dose.

If you divide incorrectly, you may inject too little or too much insulin, which may produce a level of blood sugar that is too high or too low.

More important information

• Always carry the pen with you.

• Always carry a spare pen and new needleswith you, in case of loss or breakage.

• Maintain the pen and needlesout of sight and reach of other people,especially children.

• Never sharethepen or needles with other people. This may cause infections.

• Never sharethepen with other people. Your medicine may be harmful to their health.

• People caring for patientsmustbe very careful when handling used needlesto reduce the risk of accidental punctures and infections.

Care of the pen

Treat your pen with care. Rough handling or misuse may cause inaccurate dosing, which may produce a level of blood sugar that is too high or too low.

• Do not leave the pen in the caror in any other place where it may become overheated or overcooled.

• Do not expose the pen to dust, dirt, or liquids.

• Do not wash, soak, or lubricate the pen.If necessary, wipe it with a damp cloth and a mild detergent.

• Make sure the pen does not fallor hit against hard surfaces.

If the pen falls or you suspect it may have a problem, put a new needle on it and check the insulin flow before injecting.

• Do not try to refill the pen.Once empty, it must be discarded.

Do not try to repair the penor disassemble it.